The results presented here support previous suggestions, based on experiments with isolated enzymes, that BH4 is absolutely required for cytokine-stimulated nitric oxide production in macrophages and they suggest that only a small fraction of the total intracellular BH4 pool in macrophages is utilized in the production of fully active nitric oxide synthase. (aspetjournals.org)
1.542
3-Deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase (EC 2.5.1.54) is the first enzyme in a series of metabolic reactions known as the shikimate pathway, which is responsible for the biosynthesis of the amino acids phenylalanine, tyrosine, and tryptophan. (wikipedia.org)
In enzymology, a DAHP synthase (EC 2.5.1.54) is an enzyme that catalyzes the chemical reaction phosphoenolpyruvate + D-erythrose 4-phosphate + H2O ⇌ {\displaystyle \rightleftharpoons } 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate + phosphate The three substrates of this enzyme are phosphoenolpyruvate, D-erythrose 4-phosphate, and H2O, whereas its two products are 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate and phosphate. (wikipedia.org)
Tyrosine3
These isoenzymes require a divalent metal ion and most of them are feedback regulated by the respective end product.This thesis describes studies on crystal structures of the tyrosine regulated DAHP synthase from Saccharomyces cerevisiae and a variety of its complexes. (uni-goettingen.de)
A complex of DAHP synthase, manganese(II) and tyrosine reveals the effector binding pocket of this enzyme family. (uni-goettingen.de)
By comparing the active and the inhibited structures of the enzyme the inhibition mechanism of the tyrosine sensitive DAHP synthase could be understood. (uni-goettingen.de)
Escherichia1
In Escherichia coli, a species of bacteria, DAHP synthase is found as three isoenzymes, each of which sensitive to one of the amino acids produced in the shikimate pathway. (wikipedia.org)
DHQS2
Dehydroquinate synthase (DHQS) is a nicotinamide adenine dinucleotide (NAD)-dependent enzyme that converts 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) into 3-dehydroquinate (DHQ). (nih.gov)
Dehydroquinate synthase (DHQS) catalyzes the conversion of DAHP to DHQ in shikimate pathway for. (systemsbiology.net)
Shikimate pathway2
Thus the amount of carbon entering the shikimate pathway can be controlled by inhibiting DAHP synthase from catalyzing the reaction that forms DAHP. (wikipedia.org)
The first common step in biosynthesis for these amino acids follows the shikimate pathway and the initial reaction, the condensation of erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) is catalyzed by the enzyme family of 3-Deoxy-arabino-heptulosonate-7-phosphate synthases (DAHP synthases). (uni-goettingen.de)
Cofactor2
It has been shown that, in general, DAHP synthases require a bivalent metal ion cofactor in order for the enzyme to function properly. (wikipedia.org)
Interleukin (IL)-1β-induced inhibition of glucose-stimulated insulin secretion in rat islets of Langerhans is mediated in part by nitric oxide (NO). The NO synthase cofactor 5,6,7,8-tetrahydrobiopterin (BH4) supports NO synthesis in many cell types and IL-1β-induced NO generation and inhibition of insulin secretion have been previously correlated with intracellular BH4 levels in rat insulinoma cells. (brighton.ac.uk)
Inhibition3
Feedback inhibition and transcriptional control are both mechanisms of regulating carbon in bacteria, but the only mechanism of regulation found in DAHP synthase found in plants is transcriptional control. (wikipedia.org)
It was also determined that the enzyme is inhibited by inorganic phosphate through noncompetitive inhibition with respect to both substrates and inhibited by DAHP through competitive inhibition with respect to phosphoenolpyruvate and noncompetitive inhibition with respect to D-erythrose 4-phosphate. (wikipedia.org)
DAHP reversed IL-1β-induced inhibition of islet insulin secretion, an effect prevented by sepiapterin. (brighton.ac.uk)
Reaction3
Forms of this enzyme differ between organisms, but can be considered DAHP synthase based upon the reaction that is catalyzed by this enzyme. (wikipedia.org)
The primary function of DAHP synthase is to catalyze the reaction of phosphoenolpyruvate and D-erythrose 4-phosphate to DAHP and phosphate. (wikipedia.org)
The reaction catalyzed by DAHP synthase is shown below. (wikipedia.org)
Inhibitor2
When the cells were stimulated in the presence of 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 biosynthesis, biopterin levels decreased by 90% within 6 hr, whereas nitrite production was essentially unaffected. (aspetjournals.org)
IL-1β-induced NO generation by BRIN cells and islets was reduced by 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of de novo BH4 synthesis. (brighton.ac.uk)
Substrate2
Anhand der Doppelkomplex-Struktur der DAHP Synthase mit Mangan(II), PEP und dem E4P-Analogon Glycerol-3-Phosphat (G3P) wurden die Bindungstaschen der zwei Substrate innerhalb des aktiven Zentrums bestimmt. (uni-goettingen.de)
Sepiapterin, the substrate for salvage pathway BH4 synthesis, reversed this inhibitory effect of DAHP in islets but not BRIN cells. (brighton.ac.uk)
Metal ion1
Studies have suggested that one metal ion bonds to each monomer of DAHP synthase. (wikipedia.org)
Activity1
In plants, as the plants progressed through the growth cycle, the activity of DAHP synthase changed. (wikipedia.org)
Image3
To the right is an image of DAHP synthase that shows the quaternary structure of DAHP synthase. (wikipedia.org)
This image shows that DAHP synthase consists of two tightly bound dimers. (wikipedia.org)
Below the first image to the right is an image of DAHP synthase that also shows quaternary structure, however this image is in a cartoon view. (wikipedia.org)
Complex1
The binding pockets for both substrates could be determined on the basis of the double complex of the DAHP synthase with manganese, PEP and the E4P analogue glyceraldehyde-3-phosphate (G3P). (uni-goettingen.de)
Structure1
The quaternary structure of DAHP synthase consists of two tightly bound dimers, which means that DAHP synthase is a tetramer. (wikipedia.org)
Synthetase1
Class-II DAHP synthetase family [Interproscan]. (ntu.edu.sg)
Phospho-2-dehydro-3-deoxyheptonate aldolase1
This model represents the class II family of 3-deoxy-7-phosphoheptulonate synthase, aka phospho-2-dehydro-3-deoxyheptonate aldolase, as found in plants and some bacteria. (nih.gov)
Shikimate3
3-Deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase (EC 2.5.1.54) is the first enzyme in a series of metabolic reactions known as the shikimate pathway, which is responsible for the biosynthesis of the amino acids phenylalanine, tyrosine, and tryptophan. (wikipedia.org)
In Escherichia coli, a species of bacteria, DAHP synthase is found as three isoenzymes, each of which sensitive to one of the amino acids produced in the shikimate pathway. (wikipedia.org)
Thus the amount of carbon entering the shikimate pathway can be controlled by inhibiting DAHP synthase from catalyzing the reaction that forms DAHP. (wikipedia.org)
Ions3
Metal ions are required in order for DAHP synthase to catalyze reactions. (wikipedia.org)
In DAHP synthase, it has been shown that binding site contains patterns of cysteine and histidine residues bound to metal ions in a Cys-X-X-His fashion. (wikipedia.org)
To gain further insight into the role of the metal ion and the catalytic mechanism in general, the crystal structures of several complexes between the tyrosine-regulated form of DAHP synthase from Saccharomyces cerevisiae and different metal ions and ligands have been determined. (rcsb.org)
Regulation2
Feedback inhibition and transcriptional control are both mechanisms of regulating carbon in bacteria, but the only mechanism of regulation found in DAHP synthase found in plants is transcriptional control. (wikipedia.org)
The DAHP synthases are possible targets for fungicides and represent a model system for feedback regulation in metabolic pathways. (rcsb.org)
Metal3
It has been shown that, in general, DAHP synthases require a bivalent metal ion cofactor in order for the enzyme to function properly. (wikipedia.org)
Studies have suggested that one metal ion bonds to each monomer of DAHP synthase. (wikipedia.org)
3-Deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthases are metal-dependent enzymes that catalyse the first committed step in the biosynthesis of aromatic amino acids in microorganisms and plants, the condensation of 2-phophoenolpyruvate (PEP) and d-erythrose 4-phosphate (E4P) to DAHP. (rcsb.org)